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ID PMID Title PublicationDate abstract
26047509 Expansion of Activated Peripheral Blood Memory B Cells in Rheumatoid Arthritis, Impact of 2015 Although B cell depletion therapy (BCDT) is effective in a subset of rheumatoid arthritis (RA) patients, both mechanisms and biomarkers of response are poorly defined. Here we characterized abnormalities in B cell populations in RA and the impact of BCDT in order to elucidate B cell roles in the disease and response biomarkers. In active RA patients both CD27+IgD- switched memory (SM) and CD27-IgD- double negative memory (DN) peripheral blood B cells contained significantly higher fractions of CD95+ and CD21- activated cells compared to healthy controls. After BCD the predominant B cell populations were memory, and residual memory B cells displayed a high fraction of CD21- and CD95+ compared to pre-depletion indicating some resistance of these activated populations to anti-CD20. The residual memory populations also expressed more Ki-67 compared to pre-treatment, suggesting homeostatic proliferation in the B cell depleted state. Biomarkers of clinical response included lower CD95+ activated memory B cells at depletion time points and a higher ratio of transitional B cells to memory at reconstitution. B cell function in terms of cytokine secretion was dependent on B cell subset and changed with BCD. Thus, SM B cells produced pro-inflammatory (TNF) over regulatory (IL10) cytokines as compared to naïve/transitional. Notably, B cell TNF production decreased after BCDT and reconstitution compared to untreated RA. Our results support the hypothesis that the clinical and immunological outcome of BCDT depends on the relative balance of protective and pathogenic B cell subsets established after B cell depletion and repopulation.
26728148 Characterization of copy number variants for CCL3L1 gene in rheumatoid arthritis for Frenc 2016 Aug Analyses of copy number variants (CNVs) for candidate genes in complex diseases are currently a promising research field. CNVs of C-C chemokine ligand 3-like 1 (CCL3L1) gene are candidate genomic factors in rheumatoid arthritis (RA). We investigated CCL3L1 CNVs association with a case-control study in Tunisians and a transmission analysis in French trio families. Relative copy number (rCN) of CCL3L1 gene was quantified by droplet digital PCR (ddPCR) in 100 French trio families (RA patients and their two parents) and in 166 RA cases and 102 healthy controls from Tunisia. We calculated odds ratio (OR) to investigate association risk for CCL3L1 CNVs in RA. rCN identified varied from 0 to 4 in the French population and from 0 to 7 in the Tunisian population. A significant difference was observed in the distribution of these rCNs between the two populations (p = 2.34 × 10(-10)), as when rCN from French and Tunisian RA patients were compared (p = 2.83 × 10(-5)). CNVs transmission in French RA trios allowed the characterization of genotypes with the presence of tandem duplication and triplication on the same chromosome. RA association tests highlighted a protective effect of rCN = 5 for CCL3L1 gene in the Tunisian population (OR = 0.056; CI 95 % [0.01-0.46]). Characterization of CCL3L1 CNVs with ddPCR methodology highlighted specific CN genotypes in a French family sample. A copy number polymorphism of a RA candidate gene was quantified, and its significant association with RA was revealed in a Tunisian sample.
27522716 [Subpopulations of Regulatory T-lymphocytes in the Peripheral Blood of Patients with Rheum 2016 BACKGROUND: Rheumatoid arthritis (RA) is an inflammatory rheumatic disease associated with a dysfunction of the T cell-mediated tolerance and leading to the disability of working population. The regulatory CD4' T cells play an important role in the regulation of autoimmunity and can suppress immune responses. With that, there is no consensus on the content of these lymphocytes and their role in the pathogenesis of RA. Objective: The aim of the study was to assess the content ofperipheral blood regulatory Tcells (Treg) according to the expression of membrane markers CD4, CD25, CD127 and intracellular FOXP3 marker, as well as the expression of two functional molecules (CTLA-4 and CCR4) in Treg cells of patients with RA. METHODS: Peripheral blood samples of RA patients (median age 65,5 years [54;68,3) and healthy controls (median age 58 years [44; 66]) were analyzed. Cell count and the expression level of molecules were assessed by flow cytometry. RESULTS: Peripheral blood samples of 36 RA patients and 20 healthy donors were analyzed. The number of the cells with Treg-associated phenotypes CD4⁺CD25hi and CD4⁺CD25hiCD127low/⁻ was higher in RA patients in comparison with healthy donors. Increased levels of RA CD4⁺ T cells expressing FOXP3 were also observed. This may be due to increasing in the number of CD4⁺FOXP3⁺CD25⁻ lymphocytes, whereas the content of RA CD4⁺FOXP3⁺CD25⁺ Treg cells was at the level of the control. The expression of the functional molecule CTLA-4 in Treg cells of patients with RA was not different from the control, while the expression level of the chemokine receptor CCR4 which provides migration of lymphocytes at sites of inflammation and barrier tissues was significantly increased in RA patients. CONCLUSION: Increase in the levels of certain Treg-associated lymphocyte populations were detected in peripheral blood of RA patients. During the natural course of RA, alterations in the level of the chemokine receptor CCR4 might indicate the enhanced lymphocyte migration.
25209067 Interaction between dietary sodium and smoking increases the risk for rheumatoid arthritis 2015 Mar OBJECTIVE: Recent studies in animal models and on human cells have shown an effect of sodium chloride (NaCl) on Th17 cells promoting inflammation. The aim of this study was to evaluate the impact of NaCl intake on the risk of development of RA. METHODS: A nested case-control study was performed using population-based prospective data from the Västerbotten Intervention Programme. The study included 386 individuals who had stated their dietary habits as part of a community intervention programme a median of 7.7 years before the onset of symptoms of RA. For comparison, 1886 matched controls were identified from the same database and co-analysed. RESULTS: No significant association was found between sodium intake and the development of RA when all of the individuals were included. In analyses stratified for smoking status at the time of the examination, sodium intake more than doubled the risk for RA among smokers [odds ratio (OR) 2.26 (95% CI 1.06, 4.81)]. This was not observed among non-smokers. Additive interaction analysis of smoking and cases with the highest tertile of sodium intake revealed that 54% of the increased risk of developing RA from these exposures was due to interaction between them [attributable proportion 0.54 (95% CI 0.26, 0.82)]. The risk was further increased for the development of anti-CCP-positive and/or HLA shared epitope-positive RA. CONCLUSION: Although we were unable to confirm our stated hypothesis, our results that high sodium consumption among smokers was associated with the risk of RA may provide new insights into the impact of smoking in RA development.
25211402 Drug retention rates of second biologic agents after switching from tumor necrosis factor 2015 Mar OBJECTIVES: The purpose of this study was to explore drug retention rates of second biologic agents after switching from tumor necrosis factor inhibitors (TNFi) in clinical practice in patients with rheumatoid arthritis (RA) on low-dose methotrexate (MTX) or without MTX. METHODS: A total of 169 RA patients who had been withdrawn from first-course TNFi therapy and received a different TNFi or tocilizumab (TCZ) as a second biologic agent were selected from the Tsurumai Biologics Communication Registry, an observational cohort database. Retention rates of second biologic treatment were compared by the type of first TNFi and second biologic agents. RESULTS: Eighty-six patients received first-course infliximab (IFX) or adalimumab (ADA) therapy, and 83 patients received first-course etanercept (ETN) therapy. The former group had a significantly higher retention rate (IFX, 81.1%; ADA, 83.3%) of the second biologic therapy compared to the latter (56.6%, p < 0.001, log-rank test). Drug retention rates of the second biologic agent after switching from IFX/ADA were significantly higher with ETN (90.0%) and TCZ (94.7%) than with ADA/IFX (59.3%). Drug retention rates of the second biologic agent after switching from ETN were significantly higher with TCZ (75.9%) than with ADA/IFX (46.3%). The differences were significant even after adjusting for baseline clinical variables using the Cox proportional hazards model. CONCLUSIONS: Drug retention rates of IFX and ADA after switching from the first TNFi were significantly lower compared to those of ETN and TCZ in patients on low-dose MTX or without MTX.
25102365 Association of OPG gene polymorphism with susceptibility to rheumatoid arthrits in Chinese 2015 Jun AIM: To investigate the association of osteoproterin (OPG) gene polymorphisms 163A/G (rs3102735), 245T/G (rs3134069) with susceptibility to rheumatoid arthritis (RA) in Chinese Han population. OBJECTIVE: To study the correlation between the disease of rheumatoid arthritis (RA) in Chinese Han group and the association of osteoproterin (OPG) gene polymorphisms 163A/G(rs3102735) and 245T/G (rs3134069). Approaches: 205 RA patients and 171 healthy control subjects were participated into this study. Genotype analysis was conducted by polymerase chain reaction-based restriction fragment length polymorphism and was subsequently confirmed by DNA sequencing. Odd ration (OR) and 95% confidence intervals (95% CI) were calculated for the risk of genotype and allele. CONSEQUENCES: OPG gene polymorphisms 163A/G, 245T/G conformed to the Hardy-Weinberg equilibrium. The statistical differences in genotype of AA, AG, GG at 163A/G locus were founded in RA and controls. The G allele was associated with an increased risk of RA, with OR 1.219 (95% CI: 1.066-2.339). According to the observation, there are no significant differences between the RA and control groups with respect to genotype and allele frequencies of OPG gene 245T/G (χ(2)=0.734, 0.518, p>0.05). CONCLUSION: The OPG gene 163A/G SNP may be associated with the susceptibility of RA, G allele may be the risk factor for the development of RA.
26666766 High prevalence of cardiovascular comorbidities in patients with rheumatoid arthritis from 2016 Jul OBJECTIVE: To reveal any association between rheumatoid arthritis (RA) and cardiovascular comorbidities using a Japanese health insurance database. METHOD: This population-based cross-sectional study was conducted using health insurance data provided by the Japan Medical Data Center Co., Ltd. We identified 2762 RA subjects having RA diagnostic codes (ICD10 codes; M05, M060, M062-63, M068-069) with at least two physician visits more than two months apart between June 2011 and May 2012 (RA group, n = 2762). We selected age- (±5 years), sex-, and study period-matched non-RA subjects (non-RA group, n = 27,620). We compared the prevalence of cardiovascular and related comorbidities (ischemic heart diseases [IHD], cerebral infarction, hypertension [HT], dyslipidemia [DL], and diabetes mellitus [DM]) between these groups and investigated the association between RA and cardiovascular comorbidities using a conditional logistic regression analysis. RESULTS: The prevalence of all the investigated comorbidities in the RA group was significantly higher compared to the non-RA group. Odds ratios [95% confidence interval] of RA for IHD and cerebral infarction were 2.0 [1.5-2.5] and 3.1 [2.2-4.2] respectively, after adjusting for HT, DL, and DM. CONCLUSIONS: This study revealed for the first time in the Japanese population that RA was significantly associated with cardiovascular comorbidities.
27938812 Acral manifestations of paraneoplastic and collagen vascular diseases. 2017 Jan The skin often signals a number of systemic disease, making skin findings of paramount significance. Paraneoplastic diseases and collagen vascular diseases are vitally important illnesses. Paraneoplastic diseases and collagen vascular diseases may also occur with many different acral skin findings. Paraneoplastic skin diseases, associated with some cancers, are by definition nonmalignant skin disorders. These diseases can occur before, simultaneously, or after the diagnosis of cancer. Acral paraneoplastic diseases include acanthosis nigricans maligna, acquired pachydermatoglyphia, acrokeratosis paraneoplastica, palmoplantar keratoderma, and paraneoplastic nail disorders. Collagen vascular diseases include the acral skin findings of lupus erythematosus, scleroderma, dermatomyositis, and rheumatoid arthritis. Any acral skin finding may be encountered as the first finding of an undiagnosed malignancy or collagen vascular diseases. The role of the dermatologist is significant for often being the first physician to suspect a malignancy or collagen vascular disease.
25492850 Methylene tetrahydrofolate reductase genotypes frequencies: association with toxicity and 2015 Feb OBJECTIVES: The purpose of this study was to determine the genotype/allele frequencies of C677T and A1298C polymorphisms of methylenetetrahydrofolate (MTHFR) gene in Jordanian rheumatoid arthritis (RA) patients. In addition, the association between MTHFR gene C677T and A1298C polymorphisms and response to and toxicity of methotrexate (MTX) was evaluated. METHODS: 159 adult rheumatoid arthritis ent Rheumatology Clinic at The Jordan University Hospital, between December, 2011 and April, 2012 were recruited into the study. Genomic DNA was extracted from leukocytes using Wizard Genomic DNA extraction Kit. The DNA extracts were amplified by polymerase chain reaction (PCR), and the PCR products were subjected to restriction enzymes to identify the C677T and A1298C genotypes. Genotype frequencies were identified and their relationship to some measures of MTX response and toxicity were evaluated. RESULTS: The 677 TT genotype frequency was higher in RA patients (15.1%) compared to the healthy control group (5.9%) (odds ratio 3.09, 95% confidence interval (CI) 1.39-6.87, p-value=0.0056). No such differences were seen with the A1298C genotypes. The frequencies of 677T and 1298C variant alleles were 0.346 and 0.296, respectively. None of the change-in-disease-activity measurements in MTX-treated patients has a significant association with the various genotypes. There was no significant association between A1298C genotypes and "œany MTX toxicity", but there was an association between C677T polymorphism and "œany MTX toxicity" (p=0.037). In addition, there was no association between both SNPs and specific MTX adverse effects. However, some haplotypes or combinations of the C677T and A1298C genotypes were associated with certain MTX side effects. CONCLUSIONS: More data from a larger number of RA patients are needed to evaluate the role of pharmacogenetic studies of MTHFR gene in predicting MTX response and toxicity.
25243767 Dilemmas of participation in everyday life in early rheumatoid arthritis: a qualitative in 2015 PURPOSE: To explore the experiences of today's patients with early rheumatoid arthritis (RA) with respect to dilemmas of everyday life, especially regarding patterns of participation restrictions in valued life activities. METHODS: A total of 48 patients, aged 20-63, three years post-RA diagnosis were interviewed using the Critical Incident Technique. Transcribed interviews were condensed into meaningful units describing actions/situations. These descriptions were linked to ICF participation codes according to the International Classification of Functioning, Disability and Health (ICF) linking rules. RESULTS: Dilemmas in everyday life were experienced in domestic life, interpersonal interactions and relationships, community, social and civic life. Most dilemmas were experienced in domestic life, including participation restrictions in, e.g. gardening, repairing houses, shovelling snow, watering pot plants, sewing or walking the dog. Also many dilemmas were experienced related to recreation and leisure within the domain community, social and civic life. The different dilemmas were often related to each other. For instance, dilemmas related to community life were combined with dilemmas within mobility, such as lifting and carrying objects. CONCLUSIONS: Participation restrictions in today's RA patients are complex. Our results underline that the health care needs to be aware of the patients' own preferences and goals to support the early multi-professional interventions in clinical practice. Implications of Rehabilitation Today's rheumatoid arthritis (RA) patients experience participation restrictions in activities not included in International Classification of Functioning, Disability and Health (ICF) core set for RA or in traditionally questionnaires with predefined activities. The health care need to be aware of the patients' own preferences and goals to meet the individual needs and optimize the rehabilitation in early RA in clinical practice.
25660652 Intelligent use and clinical benefits of electronic health records in rheumatoid arthritis 2015 Mar In the past 10 years, electronic health records (EHRs) have had growing impact in clinical care. EHRs efficiently capture and reuse clinical information, which can directly benefit patient care by guiding treatments and providing effective reminders for best practices. The increased adoption has also lead to more complex implementations, including robust, disease-specific tools, such as for rheumatoid arthritis (RA). In addition, the data collected through normal clinical care is also used in secondary research, helping to refine patient treatment for the future. Although few studies have directly demonstrated benefits for direct clinical care of RA, the opposite is true for EHR-based research - RA has been a particularly fertile ground for clinical and genomic research that have leveraged typically advanced informatics methods to accurately define RA populations. We discuss the clinical impact of EHRs in RA treatment and their impact on secondary research, and provide recommendations for improved utility in future EHR installations.
27404002 Risk Factors and Outcomes of Nontuberculous Mycobacterial Disease among Rheumatoid Arthrit 2016 Jul 11 Increasing evidence indicates that the risk of nontuberculous mycobacteria (NTM) disease is elevated in patients with rheumatoid arthritis (RA). However, the risk factors and outcomes for NTM disease among RA patients remain unclear. We conducted a case-control study and estimated odds ratios (ORs) for RA patients with NTM disease according to comorbidities and anti-rheumatic medications by using conditional logistic regression. Prior tuberculosis history (adjusted OR (aOR) =5.58, p < 0.001), hypertension (aOR = 2.55, p = 0.013), diabetes mellitus (aOR = 3.31, p = 0.005), interstitial lung disease (aOR = 8.22, p < 0.001), chronic obstructive pulmonary disease (aOR = 8.59, p < 0.001) and exposure to oral corticosteroids in a dose-dependent manner (5- < 10 mg/day aOR = 2.51, Ptrend = 0.007) were associated with a significantly increased risk of NTM disease in RA patients. The predominant species causing NTM disease in RA patients was Mycobacterium intracellulare (46.0%). Most NTM isolates were resistant to the majority of the antibiotics that are currently available, which maybe caused treatment failure; hospitalization and mortality are increased. To prevent and treat NTM disease efficiently, we suggested that it is important to monitor the development of NTM disease in RA patients receiving therapy with corticosteroids, particularly in those with predisposing factors.
27909140 Longterm Work Productivity Costs Due to Absenteeism and Permanent Work Disability in Patie 2016 Dec OBJECTIVE: To estimate the development and potential disproportional distribution of longterm productivity costs (PC) and their determinants leading to work absenteeism and permanent work disability in working-aged patients with early rheumatoid arthritis (RA). METHODS: A cohort of subjects with early RA was created by identifying the new cases of RA from the national drug reimbursement register that had been granted a special reimbursement for their antirheumatic medications for RA from 2000-2007. The dataset was enriched by cross-linking with other national registries detailing work absenteeism days and permanent disability pensions. In the base case, the human capital approach was applied to estimate PC based on subjects' annual number of absenteeism days and incomes. Hurdle regression analysis was applied to study the determinants of PC. RESULTS: Among the 7831 subjects with early RA, the mean (bootstrapped 95% CI) annual PC per person-observation year was €4800 (4547-5070). The annual PC declined after the first year of RA diagnosis, but increased significantly in subsequent years. In addition, the PC was heavily disproportionally concentrated in a small fraction of patients with RA, because only around 20% of patients accounted for the majority of total annual PC. The initiation of active drug treatment during the first 3 months after RA diagnosis significantly reduced the cumulative PC when compared with no drug treatment. CONCLUSION: The longterm PC increased significantly in parallel with years elapsing after RA diagnosis. Further, the majority of these PC are incurred by a small proportion of patients.
26462971 Sedentary behaviour in patients with rheumatoid arthritis: A qualitative study. 2015 BACKGROUND: Despite increasing interest in investigating sedentary behaviour (SB) in the general population and in patients with rheumatoid arthritis (RA), there is little documentation of the subjective experiences of SB in patients with RA. This study aimed to examine how patients with RA describe their daily SB. METHODS: Fifteen patients with RA (10 women and 5 men) from 23 to 73 years of age and with a disease duration ranging from 4 to 27 years were interviewed following a semi-structured interview guide. Data were analysed using the content analysis method described by Graneheim. RESULTS: SB appeared in three categories covering: 1) A constant battle between good and bad days; SB could be a consequence of RA in terms of days with pronounced pain and fatigue resulting in many hours of SB. 2) Adaptation to everyday life; living with the unpredictability of RA included constant modification of physical activity level causing increase in SB, especially during periods of disease flare. Prioritizing and planning of SB also functioned as part of self-management strategies. 3) It has nothing to do with my arthritis; for some patients, SB was not related to RA, but simply reflected a way of living independent of the disease. CONCLUSIONS: SB is perceived, motivated, and performed differently in patients with RA. An individually tailored approach may be essential in understanding and encouraging patients' motivation towards sustainable change in SB and activity patterns.
26709121 Study on the frequency and risk factors of moderate-to-severe sleep apnea syndrome in rheu 2016 Sep OBJECTIVES: We aimed to investigate the frequency of moderate-to-severe sleep apnea syndrome (SAS) that possibly influences long-term prognosis in patients with rheumatoid arthritis (RA), and to analyze the risk factors for this group. METHODS: We examined respiratory disturbance index (RDI) by polysomnography in 62 hospitalized RA patients. Risk factors of moderate-to-severe SAS (RDI ≥20) were analyzed using a multivariate logistic regression analysis. RESULTS: RA was complicated by moderate-to-severe SAS in 13/62 (20.9%) cases. The highest stage of temporomandibular joint abnormality (TMJA) and a high value of health assessment questionnaire-disability index (HAQ-DI) were significant risk factors, according to the results of the multivariate logistic regression analysis (p < 0.0001 and p = 0.010, respectively). Contrary to these results, RDI was not related to the disease activity indexes of RA and other clinical characteristics. CONCLUSION: We clarified that the highest TMJA stage and a high value of HAQ-DI are novel important risk factors for moderate-to-severe SAS in RA patients.
25173347 DAS28, CDAI and SDAI cut-offs do not translate the same information: results from the Rheu 2015 Feb OBJECTIVES: . The 28-joint DAS (DAS28), clinical disease activity index (CDAI) and simplified disease activity index (SDAI) are indices frequently used to assess disease activity in RA patients. Cut-off values were defined to classify the states of RA disease activity: remission, low, moderate and high. The aim of this work was to assess disease activity states classified by DAS28, CDAI and SDAI and to analyse their agreement in the Rheumatic Diseases Portuguese Register Reuma.pt. METHODS: . A total of 2795 patients and 14 440 visits were selected from Reuma.pt for analysis. Pearson's correlation coefficients (PCCs) were calculated for the three indices. McNemar's chi-squared tests, PCCs and kappa statistics were performed to analyse and compare the distribution of visits among all disease activity states and indices. RESULTS: A strong correlation was found between the three indices throughout the 14 440 visits: r = 0.874 for DAS28/CDAI, r = 0.877 for DAS28/SDAI and r = 0.984 for CDAI/SDAI (all PCCs with P < 0.0001). However, when categorization in the different disease activity states was analysed, McNemar's chi-squared tests and PCCs revealed significant disagreement between the cut-offs of the three indices. CONCLUSION: DAS28, CDAI and SDAI cut-offs do not translate into the same clinical information in Reuma.pt. Although this might be expected for the original DAS28 cut-offs, when compared with CDAI and SDAI significant disagreement was also found for the DAS28 modified cut-offs. For visits where patients are in CDAI or SDAI remission, we also find disagreement between these two indices, which may contradict previous conclusions that acute phase reactants add little to composite disease activity indices for RA.
27239923 [Psychopharmacotherapy for depression in rheumatic patients]. 2016 AIM: To study attitude towards the disease in rheumatic patients during antidepressant therapy and during further follow-up. SUBJECTS AND METHODS: Examinations were made in 122 patients with degenerative joint and vertebral column disease (DJVCD) and in 30 patients with rheumatoid arthritis (RA) and concomitant affective disorders during antidepressant therapy for 3 months. RESULTS: Statistically significant differences were found between all components of the type of attitude towards disease (TATD) in patients with DJVCD or RA before the use of antidepressants. In the patients with RA, the mean value of adaptive types of TATD was significantly lower and that of disadaptive types significantly higher. After 3 months of treatment, the TATD profiles came closer. Only three components (anosognosia, hypochondriasis, and dysphoria) in the pattern of TATD remained significantly different after 6-month therapy. CONCLUSION: According to the TATD data, both the patients with DJVCD and those with inflammatory diseases of the locomotor apparatus showed unidirectional changes in attitude towards disease with a significant increase in the adaptive components and a reduction in the disadaptive ones.
27653285 Inhibition of the TWEAK/Fn14 pathway attenuates autoimmune arthritis in a SKG mouse model. 2017 May Tumor necrosis factor-like weak inducer of apoptosis (TWEAK) is a proinflammatory cytokine that is involved in pathogenesis of abnormal or disregulated inflammation. To verify how TWEAK/fibroblast growth factor-inducible gene 14 (Fn14) signals affect development of Th17 cells in arthritis, we utilized the SKG mouse, which spontaneously develops Th17-mediated autoimmune arthritis. Fn14-Fc was administered to zymosan A-induced arthritogenic SKG mice, and the effects in vivo were examined. Destruction of cartilage and bone damage was assessed by Hematoxylin and Eosin, and safranin O staining of the affected tissues. Phenotypic analysis of cells expressing inflammatory cytokines and angiogenesis-related factors, and the expression of transcription factor STAT3 in the affected joints were determined by immunohistochemistry. Blockade of Fn14 with Fn14-Fc reduced the clinical and histologic scores of inflammatory arthritis in the mouse model of spontaneously developed chronic autoimmune arthritis. Fn14-Fc suppressed production of inflammatory cytokines and angiogenesis-promoting factors, such as vascular endothelial growth factor and matrix metalloproteinase 3. Moreover, blocking of the TWEAK signal inhibited expression of STAT3 as well as interleukin-17 and -21 produced by Th17 cells. These results implicate TWEAK as a potential molecular target for treatment or prevention of inflammatory arthritis and autoimmune diseases such as rheumatoid arthritis.
26633288 Targeting of proangiogenic signalling pathways in chronic inflammation. 2016 Feb Angiogenesis is de novo capillary outgrowth from pre-existing blood vessels. This process not only is crucial for normal development, but also has an important role in supplying oxygen and nutrients to inflamed tissues, as well as in facilitating the migration of inflammatory cells to the synovium in rheumatoid arthritis, spondyloarthritis and other systemic autoimmune diseases. Neovascularization is dependent on the balance of proangiogenic and antiangiogenic mediators, including growth factors, cytokines, chemokines, cell adhesion molecules and matrix metalloproteinases. This Review describes the various intracellular signalling pathways that govern these angiogenic processes and discusses potential approaches to interfere with pathological angiogenesis, and thereby ameliorate inflammatory disease, by targeting these pathways.
27028940 Yohimbine hydrochloride ameliorates collagen type-II-induced arthritis targeting oxidative 2017 Feb Rheumatoid arthritis (RA) is the most common type of chronic inflammatory disease which is triggered by dysfunction in the immune system which in turn affects synovial joints. Current treatment of RA with NSAIDs and DMRDs is limited by their side effect. As a result, the interest in alternative, well tolerated anti-inflammatory remedies has re-emerged. Our aim was to evaluate the antioxidant and anti-inflammatory activities underlying the anti-RA effect of Yohimbine hydrochloride (YCL) in collagen induced arthritis (CIA) in Wistar rats. The YCL was administered at doses of 5 and 10 mg kg(-1) body weight once daily for 28 days. The effects of treatment in the rats were assessed by biochemical parameter (articular elastase, LPO, GSH, catalase, SOD), hematological parameter (ESR, WBC, C-reactive protein (CRP), immunohistochemical expression (COX2, TNF-α, and NF-κB), and histological changes in joints. YCL showed anti-RA efficacy as it significantly reduced articular elastase, LPO and catalase level and ameliorates histological changes. This is in addition to its antioxidant efficacy as YCL shown a significant increase in GSH and SOD level. Also, YCL showed effective anti-inflammatory activity as it significantly decreased the expression of COX-2, TNF-α, and NF-ĸB. The therapeutic effect of YCL against RA was also evident from lower arthritis scoring and reduced hematological parameter (ESR, WBC, and C-reactive protein level). The abilities to inhibit proinflammatory cytokines and modulation of antioxidant states that the protective effect of YCL on arthritis rats might be mediated via the modulation of the immune system. © 2016 Wiley Periodicals, Inc. Environ Toxicol 32: 619-629, 2017.